The objective of the proposed research is to determine the relationship between cardiac metabolism, the cardiac calcium cycle and the development, progress and reversibility of acute heart failure. Studies with perfused working rat and guinea pig hearts will be combined with work on isolated heart mitochondria and isolated cardiac plasma membranes and sarcoplasmic reticulum. Emphasis will be placed on the role of Ca2 ion in the control of the contractile cycle of the heart, and the integration of energy demand with oxidative and glycolytic metabolism in normal hearts and hearts after different intervals of ischemia or anoxia. Studies with isolated heart mitochondria will be concerned with control of the individual steps of the citric acid cycle and the transport of metabolic anions across the mitochondrial membrane with the purpose of understanding both the basic mechanism of these events and possible aberrations induced by heart failure. Studies with the cardiac plasma membranes will concentrate on measurements of the rate and capacity of Ca2 ion binding, its interaction with other cations and possible alterations induced by phosphorylation of the membrane by cyclic AMP dependent protein kinase. These studies at different levels of cellular organization will be related to each other so that the relevance of properties exhibited by isolated organelles to control and function can be ascertained in the intact heart.